Next Article in Journal
Structure/Activity Analysis of TASK-3 Channel Antagonists Based on a 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine
Next Article in Special Issue
Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and β-Endorphin Concentrations in the Periaqueductal Gray Area in Rats
Previous Article in Journal
UBA6 and Its Bispecific Pathways for Ubiquitin and FAT10
Previous Article in Special Issue
L-Lysine as the Molecule Influencing Selective Brain Activity in Pain-Induced Behavior of Rats
Article Menu
Issue 9 (May-1) cover image

Export Article

Open AccessArticle

Modulation of SUR1 KATP Channel Subunit Activity in the Peripheral Nervous System Reduces Mechanical Hyperalgesia after Nerve Injury in Mice

1
Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, MN 55812, USA
2
Department of Biomedical Sciences, Medical School Duluth, Duluth, MN 55812, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2251; https://doi.org/10.3390/ijms20092251
Received: 22 March 2019 / Revised: 26 April 2019 / Accepted: 3 May 2019 / Published: 7 May 2019
(This article belongs to the Special Issue Molecular Mechanisms of Pain)
  |  
PDF [3452 KB, uploaded 7 May 2019]
  |     |  

Abstract

The ATP-sensitive K+ channel (KATP) is involved in hypersensitivity during chronic pain and is presumed to be a downstream target of mu opioid receptors. Multiple subtypes of KATP channels exist in the peripheral and central nervous system and their activity may be inversely correlated to chronic pain phenotypes in rodents. In this study, we investigated the different KATP channel subunits that could be involved in neuropathic pain in mice. In chronic pain models utilizing spinal nerve ligation, SUR1 and Kir6.2 subunits were found to be significantly downregulated in dorsal root ganglia and the spinal cord. Local or intrathecal administration of SUR1-KATP channel subtype agonists resulted in analgesia after spinal nerve ligation but not SUR2 agonists. In ex-vivo nerve recordings, administration of the SUR1 agonist diazoxide to peripheral nerve terminals decreased mechanically evoked potentials. Genetic knockdown of SUR1 through an associated adenoviral strategy resulted in mechanical hyperalgesia but not thermal hyperalgesia compared to control mice. Behavioral data from neuropathic mice indicate that local reductions in SUR1-subtype KATP channel activity can exacerbate neuropathic pain symptoms. Since neuropathic pain is of major clinical relevance, potassium channels present a target for analgesic therapies, especially since they are expressed in nociceptors and could play an essential role in regulating the excitability of neurons involved in pain-transmission. View Full-Text
Keywords: neuropathy; KATP channels; SUR1; Kir6.2; analgesia; spinal nerve ligation neuropathy; KATP channels; SUR1; Kir6.2; analgesia; spinal nerve ligation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Luu, W.; Bjork, J.; Salo, E.; Entenmann, N.; Jurgenson, T.; Fisher, C.; Klein, A.H. Modulation of SUR1 KATP Channel Subunit Activity in the Peripheral Nervous System Reduces Mechanical Hyperalgesia after Nerve Injury in Mice. Int. J. Mol. Sci. 2019, 20, 2251.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top